Abstract：
:HIV-1 capsid plays multiple key roles in viral replication, and inhibition of capsid assembly is an attractive target for therapeutic intervention. Here, we report the atomic-resolution structure of capsid protein (CA) tubes, determined by magic-angle spinning NMR and data-guided molecular dynamics simulations. Functionally important regions, including the NTD β-hairpin, the cyclophilin A-binding loop, residues in the hexamer central pore, and the NTD-CTD linker region, are well defined. The structure of individual CA chains, their arrangement in the pseudo-hexameric units of the tube and the inter-hexamer interfaces are consistent with those in intact capsids and substantially different from the organization in crystal structures, which feature flat hexamers. The inherent curvature in the CA tubes is controlled by conformational variability of residues in the linker region and of dimer and trimer interfaces. The present structure reveals atomic-level detail in capsid architecture and provides important guidance for the design of novel capsid inhibitors.
journal_name
Nat Struct Mol Bioljournal_title
Nature structural & molecular biologyauthors
Lu M,Russell RW,Bryer AJ,Quinn CM,Hou G,Zhang H,Schwieters CD,Perilla JR,Gronenborn AM,Polenova Tdoi
10.1038/s41594-020-0489-2subject
Has Abstractpub_date
2020-09-01 00:00:00pages
863-869issue
9eissn
1545-9993issn
1545-9985pii
10.1038/s41594-020-0489-2journal_volume
27pub_type
杂志文章abstract：:The spliceosome is thought to undergo a conformational change between the two catalytic steps of precursor messenger RNA splicing, although the specific events in this transition are poorly understood. We previously proposed a two-state model of splicing in which the conformations required for the first and second ste...
journal_title：Nature structural & molecular biology
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abstract：:The association of Zika virus (ZIKV) infections with microcephaly has resulted in an ongoing public-health emergency. Here we report the crystal structure of a C-terminal fragment of ZIKV nonstructural protein 1 (NS1), a major host-interaction molecule that functions in flaviviral replication, pathogenesis and immune ...
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journal_title：Nature structural & molecular biology
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journal_title：Nature structural & molecular biology
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